Dataset Information

A Randomised Phase I Study to Assess the Safety, Tolerability and Pharmacokinetics of Palovarotene Ophthalmic Solution.

ABSTRACT:

Background and objective

Palovarotene, a selective retinoic acid receptor γ agonist, is under investigation for the treatment of dry eye disease. This study aimed to determine the ocular and systemic safety, tolerability and pharmacokinetics of palovarotene ophthalmic solution (PVO-OS) in healthy adults.

Methods

This was a randomised, vehicle-controlled phase I study (NCT04762355; retrospectively registered). Participants received either PVO-OS (at 0.025, 0.05 or 0.10 mg/mL) or a vehicle (placebo-to-match PVO-OS) once-daily or twice-daily for seven consecutive days. Safety was assessed by ocular and systemic assessments. Blood samples for pharmacokinetic assessments were collected before and after dose administration.

Results

Thirty-six participants were randomised to PVO-OS and 12 to the vehicle. Overall, 89 treatment-emergent ocular adverse events (TEOAEs) were reported by 22 participants (61.1%) receiving PVO-OS and ten TEOAEs were reported by five participants (41.7%) receiving the vehicle. Erythema, irritation and skin dryness of the eyelid were the most common TEOAEs in participants receiving PVO-OS. The incidence of TEOAEs and eyelid-related findings in the PVO-OS groups increased with ascending dose and frequency compared with participants treated with the vehicle. All TEOAEs were mild (96.6%) or moderate (3.4%) and resolved without sequelae. Plasma palovarotene concentrations were generally measurable for up to 3-4 h for 0.025 mg/mL and 0.05 mg/mL and up to 12 h for 0.10 mg/mL dose regimens, independent of the frequency of administration.

Conclusions

PVO-OS was generally well tolerated at doses up to and including 0.10 mg/mL twice daily. Similar pharmacokinetic profiles were observed for the once-daily and twice-daily regimens following multiple ascending doses of PVO-OS.

SUBMITTER: Foster WJ

PROVIDER: S-EPMC9985528 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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Publications

A Randomised Phase I Study to Assess the Safety, Tolerability and Pharmacokinetics of Palovarotene Ophthalmic Solution.

Foster William J WJ Strahs Andrew L AL Small Kent W KW Roach James M JM

Drugs in R&D 20221221 1

<h4>Background and objective</h4>Palovarotene, a selective retinoic acid receptor γ agonist, is under investigation for the treatment of dry eye disease. This study aimed to determine the ocular and systemic safety, tolerability and pharmacokinetics of palovarotene ophthalmic solution (PVO-OS) in healthy adults.<h4>Methods</h4>This was a randomised, vehicle-controlled phase I study (NCT04762355; retrospectively registered). Participants received either PVO-OS (at 0.025, 0.05 or 0.10 mg/mL) or a ...[more]

PMID: 36542308

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Dataset Information

A Randomised Phase I Study to Assess the Safety, Tolerability and Pharmacokinetics of Palovarotene Ophthalmic Solution.

Background and objective

Methods

Results

Conclusions

Publications

A Randomised Phase I Study to Assess the Safety, Tolerability and Pharmacokinetics of Palovarotene Ophthalmic Solution.

Similar Datasets

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